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A major UK patient trial of a new biomarker testing protocol for sepsis, led by University of Manchester researchers, has shown it is possible to safely stop antibiotic treatment earlier than current care.

The duration reduction of around 10% could provide significant cost savings to health systems, limit unwanted drug side-effects, reduce overtreatment and reduce the development of antimicrobial resistance in individuals, across communities and internationally.

The study was commissioned and funded by the National Institute for Health and Care Research (NIHR), and its leading partners were The University of Manchester, Northern Care Alliance NHS Foundation Trust and Warwick Medical School鈥檚 Clinical Trials Unit,  who specialise in research in emergency and critical care.

Chief investigator Paul Dark, Professor of Critical Care at the University of Manchester will present the findings to a global online audience at the prestigious this week (10/12/24), where it will be scrutinised and debated by some of the world鈥檚 leading experts in the field.

The research team are also to publish their peer reviewed findings in JAMA-  one of the world鈥檚 leading medical  journals today

According to the charity Sepsis Research FEAT, around 50,000 people are estimated to die of sepsis in the UK each year, which develops when the body's immune system overreacts to an infection and starts attacking its own tissues and organs.

Accounting for 100,000 hospital admissions a year in the UK, it is estimated that there are 49 million cases and 1 million deaths a year globally.

Recognising sepsis and starting antibiotics  early are crucial but until now the recommended duration of such treatment has been uncertain.

The only available option recommended for doctors currently is to use their judgement  to decide when to discontinue the potent  broad spectrum antibiotics, usually reserved to treat the condition.

The new decision support system is based on a simple blood test, carried out daily and available in most  NHS hospital laboratories.

It tests for levels of a circulating protein called procalcitonin (PCT), which is produced as part of the body鈥檚 immune system responses to bacterial infections.

Higher levels indicate a greater likelihood of bacterial infection and sepsis, with subsequent falling levels indicating favourable responses to treatments

A computer automated response, based on the PCT levels from the blood test,    advises doctors whether to discontinue antibiotic treatment or not.  A further commonly measured circulating inflammation protein (C-reactive protein or CRP) was also tested.

The randomized controlled trial was based at 41 intensive care units across the UK, involving 2,760 adults from January 2018 to June 2024.

It compared 918 patients on a  PCT protocol with 924 patients on a  C-reactive protein (CRP) and 918 patients on current standard care.

Clinicians responsible for managing patients received daily standardized written advice on either standard care or on PCT or CRP biomarker-guided antibiotic discontinuation.

The protocols in the study were uniquely designed to  conceal laboratory test results  from clinical  staff to reduce potential bias and patients were randomly assigned to one of the three groups.

The team found that a PCT protocol reduced total antibiotic duration by 10% and all-cause mortality, a key patient safety measure, was the same as standard care .

There was no difference in total antibiotic duration between standard care and CRP protocols..

Professor Dark, who is also an NHS Consultant in Critical Care Medicine at Salford Royal, said: 鈥淭his simple protocol, if implemented, could significantly change the way sepsis is treated and safely help to combat antimicrobial overuse and resistance-  one of the world鈥檚 leading health challenges.

鈥淚t is also a powerful illustration of how precision medicine can make a real difference to patient care  when treatment is tailored to  individual test results  of each patient.

鈥淚t鈥檚 also important to acknowledge that this study would not have been possible without the generous contribution  of patients with this life threatening condition who like all of us, are committed to finding better ways to deal with sepsis.鈥�

He added: 鈥淪epsis has been at the forefront of policy makers minds ever since the publication of 2013 Health Service Ombudsman report which focused on sepsis patients who were not treated urgently enough.

鈥淓ver since then, developing better diagnostics and treatment guidance for GPs and hospital clinicians to help them recognise sepsis at an early stage has been a national priority.

鈥淭his trial has been planned to address NICEs recommendations so that its results will inform their future guidance on antibiotic duration in sepsis.鈥�

Sepsis Research FEAT trustee Beth Budgen developed sepsis as a result of a seemingly innocuous Strep A infection on Christmas Day 2022, resulting in quadruple amputations.

She said: 鈥淲ithin 24hrs I was fighting for my life and have been left with life changing injuries as a result. If this can happen to me, it really can happen to anyone. It really is that scary

鈥淭he University of Manchester study is one of several significant projects currently being undertaken in the UK in the field of antibiotic treatment for sepsis patients - an extremely important area of research which Sepsis Research FEAT fully endorses.

鈥淭he priority setting partnership exercise that the charity recently completed with the James Lind Alliance will also now be crucial in ensuring that the best research into sepsis takes place UK-wide.鈥�

Professor Gavin Perkins, Warwick CTU Trial Lead said: 鈥淪epsis claims tens of thousands of lives each year in the UK.  The findings from ADAPT-sepsis will help doctors ensure that critically ill patients with severe infections get the right duration of treatment with life-saving antibiotics.鈥�

• Critically ill patients recruited to the trial had already commenced antibiotics for sepsis, so the study does not provide evidence for biomarker use in initiating antibiotic therapy.
• The University of Manchester, University of Warwick and Northern Care Alliance NHS Foundation Trust researchers would like to thank the NIHR Clinical Research Network (CRN) for help delivering the study in the NHS and the NIHR Health Technology Assessment Programme for funding the trial.  The collaborative  co-investigator  funded team  in this national study are linked here    .  We would also like to thank Abbott and Roche Diagnostics for their contracted support to assist NHS laboratories participate in the study. 
• Beth鈥檚 story is available to read in full and she also appears on the Sepsis Research FEAT  . The PSP outcomes page on their  website can be found .